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Abstract & Commentary
Source: Klebanoff MA, et al. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic trichomonas vaginalis infection. N Engl J Med 2001; 345:487-493.
This large, randomized, double-blinded trial of metronidazole vs. placebo in pregnant women with asymptomatic trichomoniasis was conducted to assess whether therapy would reduce the risk of preterm delivery. Asymptomatic pregnant women between 8-23 weeks gestation were screened at 15 sites for Trichomonas vaginalis by culture of vaginal secretions. After exclusions were accounted for, 617 women with trichomoniasis who were 16-23 weeks gestation were randomized to receive two 2g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. The women were treated a second time with the same two-dose regimen at 24-29 weeks gestation. The primary outcome was delivery before 37 weeks of gestation. The two groups were similar in terms of numerous characteristics measured at randomization. Approximately 90% were black, about 76% never married, and the average age was 22 years. Both groups were similar in their compliance with the medication, but side effects were significantly more common in the metronidazole group.
Delivery occurred before 37 weeks gestation in 19% of women in the metronidazole group and in 10.7% in the placebo group (relative risk, 1.8; 95% CI 1.2-2.7; P = 0.004). Most of the difference was due to an increase in the rate of spontaneous preterm labor in the metronidazole group (10.2% vs 3.5%; relative risk, 3.0; 95% CI, 1.5-5.9). In the 529 women who had follow-up cultures, T.vaginalis persisted in 65% of women who received placebo and 7% of women who received metronidazole.
Comment by Stephanie B. Abbuhl, MD, FACEP
As with many studies, this large, well-designed, randomized trial raised as many questions as it answered. The significant finding was that, despite the fact that infection with T.vaginalis has been associated with an increase in adverse outcomes of pregnancy, treatment with metronidazole did not prevent preterm delivery. In fact, there was an increase in the rate of spontaneous preterm labor in the metronidazole group, and this unanticipated result led to the cessation of the study.
The results of this study are consistent with results from the same researchers in a previous trial of metronidazole therapy for bacterial vaginosis (BV).1 The BV study found that treating pregnant women for asymptomatic BV with metronidazole did not reduce the risk of preterm birth, despite its effectiveness in eliminating BV. However, preterm delivery was more frequent only in a subgroup of women with both BV and trichomonas who received metronidazole. An increase in preterm delivery has also been observed in pregnant women with BV who were treated with clindamycin cream.2 In still another trial, a regimen of metronidazole and erythromycin increased the occurrence of preterm delivery among women who did not have BV, but reduced it in those who had BV.3 As a possible explanation for these findings, the authors suggest that there may be a group of women in whom the risk of adverse outcomes of pregnancy somehow is increased by antibiotic treatment, although the reasons for this are unclear. In addition, it seems doubtful that the association of metronidazole treatment with an increased risk of preterm delivery was due to the metronidazole itself. If this were the case, the effect most likely would have been seen earlier, instead of at 35-36 weeks gestation, when the outcome differences became significant.
In the emergency department we now are confronted with a clinical dilemma. Do we treat pregnant patients who have trichomoniasis? The easy answer is that if they are asymptomatic, probably not. There does not seem to be any reason to look routinely at wet mounts in pregnant women without vaginal symptoms.
However, if a pregnant woman is symptomatic, the answer is less clear. This study excluded women with vaginal symptoms, who presumably were treated but not reported on. Until there is more research to guide us, we will be weighing the risks and benefits on a case-by-case basis or deferring the decision to the patient’s obstetrician in a follow-up visit. After discussing this study, several OB-GYN colleagues say they still would consider treatment for women who are symptomatic.
(Dr. Abbuhl, Medical Director, Department of Emergency Medicine, The Hospital of the University of Pennsylvania; Associate Professor of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, is on the editorial board of Emergency Medicine Alert.)
1. Carey JC, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. N Engl J Med 2000;342:534-540.
2. Joesoef MR, et al. Intravaginal clindamycin treatment for bacterial vaginosis: Effect on preterm delivery and low birth weight. Am J Obstet Gynecol 1995; 173:1527-1531.
3. Hauth JC, et al. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med 1995;333: 1732-1736.